Identification of prognostic biomarkers in gastric cancer using endoscopic biopsy samples.
Endoscopic biopsy prior to chemotherapy provides an opportunity for studying biomarkers to predict the overall survival in gastric cancer patients. This prospective study was performed to identify prognostic biomarkers in patients with unresected gastric cancer. Fifty-nine cases of chemotherapy-naive metastatic gastric cancer were enrolled in this study. A microarray analysis was performed using 40 biopsy samples to identify candidate genes whose expressions might be correlated with the overall survival. After adjusting for clinical covariates based on a multivariate analysis, the identified genes were validated using real-time reverse transcription polymerase chain reaction (RT-PCR) analysis in 19 independent validation samples. Ninety-eight candidate genes whose expression levels were significantly correlated with the overall survival were identified using a microarray analysis based on a proportional hazards model (P < 0.005). Multivariate analysis was performed to assess 10 of these genes, and the results yielded a statistical significance level for DACH1 and PDCD6. We further evaluated these two genes in independent samples using real-time RT-PCR and found that lower mRNA expression levels of PDCD6 were correlated significantly with a poor overall survival. We identified PDCD6 as a prognostic biomarker in patients with unresected gastric cancer using endoscopic biopsy samples. Our PCR-based single gene prediction strategy successfully predicted the overall survival and may lead to a better understanding of this disease subgroup.
Yamada
Yasuhide
Y
Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Arao
Tokuzo
T
Gotoda
Takuji
T
Taniguchi
Hirokazu
H
Oda
Ichiro
I
Shirao
Kuniaki
K
Shimada
Yasuhiro
Y
Hamaguchi
Tetsuya
T
Kato
Ken
K
Hamano
Tetsutaro
T
Koizumi
Fumiaki
F
Tamura
Tomohide
T
Saito
Daizo
D
Shimoda
Tadakazu
T
Saka
Makoto
M
Fukagawa
Takeo
T
Katai
Hitoshi
H
Sano
Takeshi
T
Sasako
Mitsuru
M
Nishio
Kazuto
K
D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005743:Gastrectomy; D005773:Gastroscopy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; C486747:DACH1 protein, human; D005136:Eye Proteins; C097753:PDCD6 protein, human; D014157:Transcription Factors